Epilepsy, seizure, neuromodulation

Providing clinicians with objective outcomes of neuromodulation therapy is a key unmet need, especially in emerging areas such as epilepsy and mood disorders. These diseases have episodic behavior and circadian/multidien rhythm characteristics that are difficult to capture in short clinical follow-ups. This work presents preliminary validation evidence for an implantable neuromodulation system with integrated physiological event monitoring, with an initial focus on seizure tracking for epilepsy. The system was developed to address currently unmet requirements for patients undergoing neuromodulation therapy for neurological disorders, specifically the ability to sense physiological data during stimulation and track events with seconds-level granularity...

Closed-loop brain-implantable neuromodulation devices are a new treatment option for patients with refractory epilepsy. Seizure detection algorithms implemented on such devices are subject to strict power and area constraints. Deep learning methods, though very powerful, tend to have high computational complexity and thus are typically impractical for resource-constrained neuromodulation devices. In this paper, we propose a compact and hardware-efficient one-dimensional convolutional neural network (1D CNN) structure for patient-specific early seizure detection...

The role of thalamocortical circuits in memory has driven a recent burst of scholarship, especially in animal models. Investigating this circuitry in humans is more challenging. And yet, the development of new recording and stimulation technologies deployed for clinical indications has created novel opportunities for data collection to elucidate the cognitive roles of thalamic structures. These technologies include stereoelectroencephalography (SEEG), deep brain stimulation (DBS), and responsive neurostimulation (RNS), all of which have been applied to memory-related thalamic regions, specifically for seizure localization and treatment...

Neuromodulation by means of vagus nerve stimulation (VNS) therapy, reduces seizure frequency and improves quality of life in subjects with drug-resistant epilepsy (DRE), yet its molecular mechanism remains unclear. This study investigates the impact of chronic VNS on lipid bioactive metabolites and fatty acids (FA) in the plasma and red blood cells of seven subjects with DRE. By measuring expression levels of peroxisome proliferator-activated receptor α (PPARα) and sirtuin1 (SIRT1) genes - key regulators in energy and lipid metabolism - and lipid profiles before and after various stages of VNS, this study identifies potential mechanisms by which VNS may reduce seizure frequency...

Epilepsy is the most common brain disorder around the world. The main treatments of epilepsy are through drug treatment or epilepsy surgery. However, examples of EEG-based neuromodulation treatments, such as Vagus nerve stimulation (VNS), thalamic deep brain stimulation (DBS), and responsive neuro-stimulation (RNS), are also promising therapeutic methods nowadays. The aim of the paper is to recognize the effectiveness and potential risks of the three techniques. By carrying out randomized multicenter double-blind trials, this research studied the effectiveness of VNS, RNS, and DBS by measuring the median seizure reduction rate, rate of the responder, and proportion of seizure-free patients; the sudden unexpected death in epilepsy (SUDEP) of the treated patients; and the possible side effects that each treatment may cause...

Epilepsy is one of the most common neurological diseases in both adults and children. Despite improvements in medical care, 20 to 30% of patients are still resistant to the best medical treatment. The quality of life, neurologic morbidity, and even mortality of patients are significantly impacted by medically intractable epilepsy. Nowadays, conservative therapeutic approaches consist of increasing medication dosage, changing to a different anti-seizure drug as monotherapy, and combining different antiseizure drugs using an add-on strategy...

BACKGROUND: Status epilepticus is a life-threatening condition that is defined as refractory (RSE) when the seizure activity continues despite treatment with benzodiazepine and a second appropriate treatment. Super refractory status epilepticus (SRSE) is an RSE that persists or recurs for ≥24 h. Few papers have reported the outcomes of pediatric patients affected by RSE and SRSE and treated with neuromodulation therapies. Vagus nerve stimulation (VNS) is an approved treatment for drug-resistant epilepsy...

Status epilepticus (SE) is a life-threatening condition and medical emergency which can have lifelong consequences, including neuronal death and alteration of neuronal networks, resulting in long-term neurologic and cognitive deficits in children. When standard pharmacological treatment for SE is not successful in controlling seizures, the condition evolves to refractory SE (rSE) and finally to super-refractory SE (srSE) if it exceeds 24 h despite using anaesthetics. In this systematic review, we present literature data on the potential uses of clinical neuromodulation techniques for the management of srSE in children, including electroconvulsive therapy, vagus nerve stimulation, and deep brain stimulation...

Epilepsy surgery is a potentially curative treatment of drug-resistant epilepsy that has remained underutilized both due to inadequate referrals and incomplete localization hypotheses. The complexity of patients evaluated for epilepsy surgery has increased, thus new approaches are necessary to treat these patients. The paradigm of epilepsy surgery has evolved to match this challenge, now considering the entire seizure network with the goal of disrupting it through resection, ablation, neuromodulation, or a combination...

Current applications of neurostimulation for generalized epilepsy use a one-target-fits-all approach that is agnostic to the specific epilepsy syndrome and seizure type being treated. The authors describe similarities and differences between the 2 "archetypes" of generalized epilepsy-Lennox-Gastaut syndrome and Idiopathic Generalized Epilepsy-and review recent neuroimaging evidence for syndrome-specific brain networks underlying seizures. Implications for stimulation targeting and programming are discussed using 5 clinical questions: What epilepsy syndrome does the patient have? What brain networks are involved? What is the optimal stimulation target? What is the optimal stimulation paradigm? What is the plan for adjusting stimulation over time?...

Intracranial neuromodulation is an evolving therapy for patients with drug-resistant epilepsy (DRE). Deep brain stimulation (DBS) is now available as a therapy for patients with DRE and focal-onset seizures in select health care systems; however, there remains a substantial need of efficacy data before DBS can be more widely adopted into routine clinical practice. This review and commentary focuses on a particular shifting paradigm: DBS as a therapy for children with generalized-onset seizures.

Deep brain stimulation has demonstrated efficacy in reducing seizure frequency in patients with drug-resistant epilepsy who may otherwise not be candidates for other surgical procedures. Recently, a clinical device that can monitor neural activity in the form of local field potentials around the deep brain stimulator lead implant site has been introduced. While this technology has been clinically adopted in other disorders treated with deep brain stimulation, such as Parkinson's disease, its application in epilepsy remains unclear...

Since the late nineteenth century, the prevailing view of epilepsy surgery has been to identify a seizure focus in a medically refractory patient and eradicate it. Sadly, only a select number of the many who suffer from uncontrolled seizures benefit from this approach. With the development of safe, efficient stereotactic methods and targeted surgical therapies that can affect deep structures and modulate broad networks in diverse disorders, epilepsy surgery in children has undergone a paradigmatic evolutionary change...

Repetitive stimulation procedures are used in neuromodulation techniques to induce persistent excitatory or inhibitory brain activity. The directivity of modulation is empirically regulated by modifying the stimulation length, interval, and strength. However, bidirectional neuronal modulations using ultrasound stimulations are rarely reported. This study presents bidirectional control of epileptiform activities with repetitive transcranial-focused ultrasound stimulations in a rat model of drug-induced acute epilepsy...

Recently, precision medicine has attracted much attention in the management of epilepsies, but it remains unclear if the increasingly utilized ketogenic diet approaches can truly be considered precision medicine in all epilepsy treatment. Currently, it is the standard treatment for patients with GLUT1 deficiency and the latest NICE guidelines highlight ketogenic diet as a therapeutic option for multi-drug resistant epilepsy patients. Ketogenic diet is presumed to be a precision medicine tool when applied to the treatment of seizures secondary to GLUT1 transporter deficiency...

The locus coeruleus (LC) is a small brainstem nucleus and is the sole source of noradrenaline in the neocortex, hippocampus and cerebellum. Noradrenaline is a powerful neuromodulator involved in the regulation of excitability and plasticity of large-scale brain networks. In this study, we performed a detailed assessment of the activity of locus coeruleus neurons and changes in noradrenergic transmission during acute hippocampal seizures evoked with perforant path stimulation, using state-of-the-art methodology...

PURPOSE: The data resulting from epilepsy surgical evaluation are occasionally unclear in cases of mesial temporal lobe (MTL) epilepsy. Long-term intracranial EEG (iEEG) collected by the Responsive Neurostimulation (RNS) System may be an approach for capturing additional seizure data while treating patients with neurostimulation. We reviewed iEEG seizure lateralization and clinical outcomes in bilateral MTL patients at University of Utah. METHODS: Long-term RNS System iEEG seizure lateralization was compared with pre-RNS System lateralization obtained during surgical evaluation...

OBJECTIVE: Neurostimulation is an emerging treatment for patients with drug-resistant epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model...

Stress has been identified as a major contributor to human disease and is postulated to play a substantial role in epileptogenesis. In a significant proportion of individuals with epilepsy, sensitivity to stressful events contributes to dynamic symptomatic burden, notably seizure occurrence and frequency, and presence and severity of psychiatric comorbidities [anxiety, depression, posttraumatic stress disorder (PTSD)]. Here, we review this complex relationship between stress and epilepsy using clinical data and highlight key neurobiological mechanisms including the hypothalamic-pituitary-adrenal (HPA) axis dysfunction, altered neuroplasticity within limbic system structures, and alterations in neurochemical pathways such as brain-derived neurotrophic factor (BNDF) linking epilepsy and stress...

Epileptic encephalopathies constitute a group of severe epileptic disorders characterized by intractable seizures and cognitive regression. Beyond the hallmark neurological manifestations, these disorders frequently exhibit associated respiratory dysfunction, which is increasingly recognized as a critical aspect of their pathophysiology. Respiratory abnormalities in epileptic encephalopathies encompass a spectrum of manifestations, ranging from subtle alterations in breathing patterns to life-threatening events such as apneas and hypoventilation...